2h,5h-pyrano(3,2-e)(1)benzo-pyran-4(3h),5-diones

ABSTRACT

THE PRESENT INVENTION IS CONCERNED WITH THE CONDENSATION OF AN ALDEHYDE OF THE FORMULA:   R&#39;&#39;-CHO   WITH A PYRONE OR COUMARIN COMPOUND OF THE FORMULA:   3-(R-CH2-CO-),4-HO,5-R&#34;,6-R&#34;&#39;&#39;-2H-PYRAN-2-ONE   TO OBTAIN NOVEL PRODUCTS OF THE FOLLOWING FORMULA:   2-R&#39;&#39;,3-R,7-R&#34;&#39;&#39;,8-R&#34;-3,4-DIHYDRO-2H,5H-PYRANO(4,3-B)PYRAN-   4,5-DIONE   IN THE ABOVE AND SUCCEEDING FORMULAE IN THE PRESENT SPECIFICATION AND CLAIMS, R REPRESENTS ALKYL OF FROM 1 TO 10, BOTH INCLUSIVE, CARBON ATOMS OR A PHENYL RADICAL OF THE FORMULA:   (Z)N-PHENYL   WHEREIN Z REPRESENTS METHYL, BROMO, CHLORO, OR HYDROXY AND N REPRESENTS AN INTEGER FROM 0 TO 1, BOTH INCLUSIVE; R&#39;&#39; REPRESENTS PHENYL, SUBSTITUTED PHENYL, NAPHTHYL, 9ANTHRYL, 9-PHENANTHRYL, STYRYL, 2-FURYL, 2-THIENYL, OR 1METHYL-2-PYRROLYL; AND R&#34; REPRESENTS HYDROGEN AND R&#39;&#39;&#34; REPRESENTS HYDROGEN, METHYL, OR PHENYL, OR R&#34; AND R&#39;&#39;&#34;, TAKEN TOGETHER, JOINTLY REPRESENT A FOUR-CARBON-ATOM DIVALENT RADICAL WHICH WITH THE TWO CARBON ATOMS UPON WHICH R&#34; AND R&#39;&#39;&#34; ARE SUBSTITUENTS CONSTITUTES A SIXCARBON-ATOM UNSATURATED RING.

United States Patent 3,558,658 2H,5H-PYRANO(3,2-c)(1)BENZO-PYRAN- 4(3H),5-DIONES John S. McIntyre, Sarnia, Ontario, Canada, assignor to The Dow Chemical Company, Midland, Mich., a corporation of Delaware No Drawing. Filed Mar. 3, 1967, Ser. No. 620,221 Int. Cl. A01n 9/28; C07d 21/00 U.S. Cl. 260343.2 6 Claims ABSTRACT OF THE DISCLOSURE The present invention is concerned with the condensation of an aldehyde of the formula:

i HC-R with a pyrone or coumarin compound of the formula:

to obtain novel products of the following formula:

in the above and succeeding formulae in the present specification and claims, R represents alkyl of from 1 to 10, both inclusive, carbon atoms or a phenyl radical of the formula:

i i n wherein Z represents methyl, bromo, chloro, or hydroxy and n represents an integer fro-m 0 to 1, both inclusive; R represents phenyl, substituted phenyl, naphthyl, 9'- anthryl, 9-phenanthryl, styryl, 2-furyl, 2-thienyl, or 1- methyl-Z-pyrrolyl; and R" represents hydrogen and R represents hydrogen, methyl, or phenyl, or R and R, taken together, jointly represent a four-carbon-atom divalent radical which with the two carbon atoms upon which R" and R 'are substituents constitutes a sixcarbon-atom unsaturated ring.

The products of the present invention are useful as parasiticides, particularly as agents to control the growth of fungi and bacteria, especially plant pathogenic species such as apple scab and rice blast; the products are also useful as agents to control acarids and insects.

BACKGROUND OF THE INVENTION It is known that 3-acetyl-4-hydroxy-6-methyl-2-pyrone 3,558,658 Patented Jan. 26, 1971 reacts with benzaldehyde to yield 3-cinnamoyl-4-hydroxy- 6-methyl-2-pyrone (Journal of the American Chemical Society, vol. 77, pg. 5102, 1955). A similar course of reaction is observed for the corresponding 3-acetyl-4-hydroxycournarin.

SUMMARY OF THE INVENTION It has now been found that when the pyrone or coumarin with which the benzaldehyde is reacted bears a 3-acyl group which is propionyl or phenylacetyl, rather than acetyl, the reaction follows an entirely different course which is described by the following reaction (where R is CH3 or phenyl) DESCRIPTION OF THE PREFERRED EMBODIMENTS The novel aldehyde condensation reaction of the present invention is carried out by causing a reaction between an aldehyde of the formula:

with a pyrone or coumarin compound of the formula:

The reaction results in the preparation of novel products of the formula:

In the above and succeeding formulae, R represents alkyl of from 1 to 10, both inclusive, carbon atoms or a phenyl radical of the formula:

wherein Z represents methyl, bromo, chloro, or hydroxy and n represents an integer of from to 1, both inclusive; R represents phenyl, substituted phenyl, naphthyl, 9-anthryl, '9-phenanthryl, styryl, 2-furyl, 2- thienyl, or 1-methyl-2-pyrrolyl; and R" represents hydrogen and R represents hydrogen, methyl, or phenyl, or R" and R', taken together, jointly represent a fourcarbon-atom divalent radical which with the two carbon atoms upon which R" and R" are substituents constitutes a six-carbon-atom unsaturated ring.

In the present specification and claims, the term substituted phenyl is employed to designate p-acetamidophenyl, p (dimethylamino)phenyl, p (diethylamino) phenyl, and phenyl substituted with from 1 to 2 substituents, each of which is independently selected from the group consisting of chloro, bromo, hydroxy, methoxy, or, both substituents taken together, a divalent methylenedioxy substituent.

The reaction of aldehyde and pyrone or coumarin is conveniently carried out in an inert liquid reaction medium. As such reaction media, organic liquids are typically employed; the halogenated hydrocarbons constitute a class of organic liquids preferred for this purpose. The reaction goes forward under temperatures of a wide range, such as from 30 to 200 C. More preferably, however, the reaction is conducted at temperatures of from 50 to 125 C.

The amounts of the reactants employed are not critical, some of the desired product being obtained when employing the reactants in any amounts. However, the reaction consumes the reactants in amounts representing equimolecular amounts, and the supplying of the reactants in such amounts is most economical of the starting materials.

In carrying out the reaction, the reactants are contacted with one another, typically in a reaction medium, as discussed above. The reaction proceeds readily, with the production of the desired product. The reaction mixture is frequently permitted to stand for a period of time following completion of the contacting of the reactants to assure completion of the reaction. Following any such standing period, the reaction mixture is processed to separate the product. Most typically, the reaction medium is removed by evaporation under subatmospheric pressure to separate the product. However, other methods of separation and purification can be used if desired.

The addition to the reaction mixture of a small amount of piperidine facilitates the reaction.

The following examples illustrate the best mode now known for the practice of the present invention and will enable those skilled in the art to practice the same.

4 EXAMPLE 1 2,3-diphenyl-2H,5H-pyrano 3,2-c) (1)benzopyran-4 (3H) 5 -dione 4 hydroxy 3 (phenylacetyl)coumarin (15.0 grams; 0.54 mole), benzaldehyde (5.4 milliliters; 0.054 mole), and 20 milliliters of chloroform containing 0.1 milliliter of piperidine were mixed with another and the resulting mixture refluxed overnight. The chloroform was then removed by evaporation and the resulting product residue boiled with pyridine and filtered hot to separate the desired 2,3-diphenyl-2H,5H-pyrano(3,2c) (1)benzopyran-4 (3H),5-dione product, melting at 2479 C.

EXAMPLE 2 2-pheny1-3,7-dimethyl-2H,5H-pyrano (4,3-b -pyran- 4(3H),5-dione 4 hydroxy-6-methyl-3-propionyl-2-pyrone (3.5 grams; 0.017 mole) and benzaldehyde (1.7 milliliters; 0.017 mole) were refluxed overnight in 15 milliliters of chloroform containing a trace of piperidine. The product residue was separated by evaporation of solvent and thereafter recrystallized from a large volume of methanol, yielding the desired 2-phenyl-3,7-dimethyl-2H,5H-pyrano(4,3-b)

0 pyran-4(3H),5-dione product melting at 244-6" C. Elemental analysis was carried out.

Calc. for C H O (percent): C, 71.10; H, 5.19. Found (percent): C, 71.15; H, 5.07.

Other representative products of the present invention include those identified in the following examples, in which the symbol M.W. is used as an abbreviation for the term molecular weight, and the symbol M.P. is used as an abbreviation for the term melting point. The products are prepared in accordance with the procedures of the foregoing examples.

EXAMPLES 3-28 From 4 hydroxy 3-propionylcoumarin and 3-chlorobenzaldehyde, 2 (3 chlorophenyl)-3-methyl-2H,5H-pyrano(3,2-c) (1)benZopyran-4(3H),5-dione, M.W. of 340.8.

From 4-hydroxy-3-phenylacetyl-6-methyl-2-pyrone and 2-hydroxybenzaldehyde, 2-(2-hydroxyphenyl)-3-phenyl-7- methyl 2H,5H-pyrano (4,3-b pyran-4 3H) ,S-dione Product, M.W. of 348.4.

From 4 hydroxy B-propionylcoumarin and 2-naphthaldehyde, 2-(2-naphthyl)-3-methyl-2H,5H-pyrano(3,2-c) (1)benzopyran-4(3H),5-dione product, M.W. of 356.4.

From 4 hydroxy 3 propionyl-6-methyl-2-pyrone and cinnamaldehyde, 2 styryl-3,7-dimethyl-2H,5H-pyrano(4, 3-b)pyran-4(3H),5-dione product, M.W. of 296.3.

From 4 hydroxy B-phenylacetylcoumarin and 2,4-dichlorobenzaldehyde, 2-(2,4-dichlorophenyl)-3-phenyl-2H, 5H-pyrano(3,2-c) (1)benzopyran-4(3H) ,S-dione product, M.W. of 437.3.

From 4-hydroxy-3-phenylacetyl-6-methyl-2-pyrone and 3,4-dimethoxybenzaldehyde, 2-(3,4-dimethoxyphenyl)-3 phenyl 7 methyl 2H,5H-pyrano(4,3-b)pyran-4(3H),5- dione product, M.W. of 392.4.

From 4-hydroxy-3-propionylcoumarin and 3,4-methylenedioxybenzaldehyde, 2 (3,4-methylenedioxyphenyl)-3- methyl 2H,5H pyrano(3,2-c)(1)benzopyran-4(3H),5- dione product, M.W. of 350.3.

From 4-hydroxy-3-propionyl-6-methyl-2-pyrone and 2- thiophenealdehyde, 2-thienyl-3,7-dimethyl-2H,5H-pyrano (4,3-b)pyran-4(3H),S-dione product, M.W. of 276.3.

From 4 hydroxy 3-phenylacetylcoumarin and p-acetamidobenzaldehyde, 2-(p-acetamidophenyl)-3-phenyl-2H, 5H-pyrano( 3,2-c) (1)benzopyran-4(3H) ,S-dione product, M.W. of 425.4.

From 4-hydroxy-3-propionyl-6-methyl-2-pyrone and pdiethylamino benzaldehyde, 2- (p- (diethylamino -phen yl) 3,7 dimethyl-2H,5H-pyrano(4,3-b)pyran-4(3H),5- dione product, M.W. of 341.4.

From 4 hydroxy 3-propionylcoumarin and 2-furaldehyde, 2-(2-furyl)-3-methyl-2H,5H-pyrano(3,2-c)-(1 )ben zopyran-4(3H),5-dione produce, M.W. of 296.3.

From 4-hydroxy-3-phenylacetyl-6-methyl-2 pyrone and 9-anthraldehyde, 2-(9-anthryl)-3-phenyl-7-methyl-2H,5H- pyrano(4,3 b)pyran 4(3H),5 dione product, M.W. of 432.5.

From 4 hydroxy 3-propionylcoumarin and 9-phenanthraldehyde, 2 (9-phenanthryl)-3-methyl-2H,5H-pyrano (3,2-c)(1)benzopyran-4(3H),S-dione product, M.W. of 406.4. a

From 4-hydroxy3-propionyl-6-methyl-2-pyrone and 1- methylpyrrole-2-aldehyde, 2- l-methyl-2-pyrrolyl) -3,7-dimethyl 2H,5H-pyrano (4,3-b)pyran-4-(3H),S-dione product, M.W. of 273.3.

From 4-hydroxy-3-propionylcoumarin and benzaldehyde, 2 phenyl-3-methyl-2H,5H-pyrano (3,2-c) 1)benzopyran-4(3H),5-dione product, M.P. of 1901 C.

From 4-hydroxy-3-propionyl-2-pyrone and benzaldehyde, 2-phenyl-3-rnethyl-2H,5H-pyrano(4,3-b)pyran 4- (3H),5-dione product, M.W. of 256.3.

From 4-hydroXy-3-octanoyl-6-phenyl-2 pyrone and benzaledphyde, 2,7-diphenyl 3-nheXyl-2H,5H-pyrano- (4,3-b)pyran-4(3H),S-dione product, M.W. of 402.5.

From 4-hydroxy-3-hexanoyl-2-pyrone and p-bromobenzaldehyde, 2 (p bromophenyl)-3-n-butyl-2H,5H-pyrano- (4,3-b)pyran-4(3I-I),S-dione product, M.W. of 377.3.

From 4-hydroxy-deeanoyl-6phenyl-Z-pyrone and benzaldehyde, 2,7-diphenyl-3-octyl 2H,5H pyrano(4,3-b)- pyran-4(3H),5-dione product, M.W. of 430.6.

From 4-hydroxy-3-butyryl-6-methyl-2-pyrone and benzaldehyde, 2 phenyl 3-ethyl-7-methyl 2H,5-H-pyrano- (4,3-b)pyran-4(3H),S-dione product, M.W. of 284.3.

From 4-hydroxy-3-(p-tolylacetyl)coumarin and benzaldehyde, 2-phenyl-3-p-tolyl 2H,5H pyrano(3,2-c) (1)- benzopyran-4(3H),5-dione product, M.W. of 382.4.

From 4-hydroxy-3-pheny1acetyl-2-pyrone and benzaldehyde, 2,3-diphenyl-2H,5H-pyrano(4,3-d)pyran-4-(3H),5- dione product, M.W. 318.3.

From 4-hydroxy-3- (o-chlorophenyl) acetyl) -6-methyl- 2-pyrone and Z-naphthaldehyde, 2-naphthyl-3-(o-chlorophenyl) 7 methyl-2H,5H-pyrano (4,3 b)pyran- 4(3H),S-di0ne product, M.W. of 416.9.

From 4-hydroxy-3- (p-bromophenyl) acetyl) -6-phenyl- 2-pyrone and 2-furaldehyde, 2-furyl-3-(p-bromophenyl)- 7-phenyl-2H,5H-pyrano(4,3-b)-pyran 4(3H),5 dione product, M.W. of 463.3.

From 4-hydroxy-3-( (p-hydroxyphenyl) acetyl)-coumarin and Z-thiophenealdhyde, 2 thienyl-3-(p-hydroxyphenyl)-2-H,5H-pyrano(3,2-c)(1)benzopyran 4(3H),5-

dione product, M.W. of 390.4.

From 4-hydroXy-3-phenylacetyl-6-methyl-2-pyrone and benzaldehyde, 2,3-diphenyl-7-methyl-2H,SH-pyrano(4,3- b)pyran-4(3H),5-dione product, M.P. of 241-3 C.

When one of the products of the present invention is employed as a parasiticide, the unmodified product can be utilized. However, the present invention also encompasses the utilization of the product together with a parasiticide adjuvant. In such utilization, the product can be dispersed on a finely divided solid and the resulting preparation employed as a dust. Also, a product of the present invention, or a composition comprising a product of the present invention and a finely divided solid, can be dispersed in water with the aid of a wetting agent and the resulting aqueous suspension employed as a spray. In other procedures, a product according to the present invention can be employed as the constituent of organic liquid compositions, oil-in-water or water-inoil emulsions, or water dispersions, with or without the addition of a Wetting, dispersing or emulsifying agent.

In representative operations, a treating composition containing, as sole active agent, 500 milligrams of 2,3- diphenyl-2H,5H-pyrano(3,2-c) (1)benzopyran 4(3H),5- dione per 100 milliliters of solvent was employed to treat nymphs of the lone star tick (Amblyomma americanum). Treatment was eifected by wetting the nymphs briefly with the treating composition. As a result, there was obtained a 100 percent kill and control of lone star tick.

The starting materials to be employed in the condensation reaction of the present invention are themselves prepared in known methods which comprise the acylation of the corresponding 4- hydroxy compound:

and, either concomitantly or subsequently, its rearrangement to the desired starting material. Thus, the 4-hydroXy compound is reacted with the desired acyl halide, of the formula halogen-ii-CEh-R the resulting 4-acyl product is then rearranged to the desired starting material by contacting it with sulfuric acid or pyridine catalyst. Alternately, the acylation is carried out in the presence of the catalyst, in which instance, the desired starting material is obtained directly. Good results are obtained when employing equimolecular proportions of 4-hydroxy compound and acyl halide, or an excess of the acyl halide; and when employing the catalyst in a minor, catalytic amount. The reactions are preferably carried out at temperatures of from 75 to C. and in an organic liquid solvent.

I claim:

1. Compound of the formula:

wherein R represents alkyl of l to 10 carbon atoms, inclu sive, or a phenyl radical of the formula:

wherein Z represents methyl, bromo, chloro, or hydroxy and n represents an integer of 0 or 1; and R represents naphthyl, 9-anthryl, 9-phenanthryl, styryl, 2-furyl, 2-thienyl, 1- methyl 2 pyrrolyl or a phenyl radical of the formula:

7 8 6. Method for the preparation of a compound of the which method comprises reacting at a temperature of formula: from 30 to 200 C., a first reactant of the formula:

wherein R represents alkyl 1 to 10 carbon atoms, incluwlth second reactant of the formula:

sive, or a phenyl radical of the formula:

wherein Z represents methyl, bromo, chloro, or hydroxy and n represents an integer of 0 or 1; and R represents naphthyl, 9-anthryl, 9-phenanthryl, styryl, 2-furyl, 2-thienyl, l-methyl-Z-pyrrolyl or a phenyl radical of the JOHN D RANDOLPH Primary Examiner formula:

5 C. M. SHURKO, Assistant Examiner 20 References Cited Woods, J. Org. Chem. 27: 6968 (1962).

US. Cl. X.R. 

